Kibdelone C part II

05 August 2011 - Total synth.

Cibdelone C Butler II  Meanwhile at the University of Texas, Butler et al. came up with their own scheme for Kibdelone C (See earlier post here). Here are the highlights.

The junction of aldehyde 1 and vinyl iodide 2 can be observed sort of in the Porco effort but the similarities end there. Methyl lithium was required to deprotonate the alcohol group and t-BuLi formed the vinyl lithium intermediate. The reaction type is a nucleophilic addition. Dess-Martin oxidation with acidic acetone and t-BuOH removed three protective groups (MOM = methoxymethyl ether), TBS = tert-butyldimethylsilyl) in one go, closed the ring to tetrahydroxanthone 4 with protection of two hydroxyl groups as an acetonide.

Bromide 5 was functionalized with an alkyne group in one Sonogashira coupling (Pd(PhCN)2)Cl2, (tBu)3P.HBF4, CuI, diisopropylamine) with TIPS protected acetylene (see: trimethylsilylacetylene) followed by TBAF deprotection and then in another Sonogashira 6 was coupled with 4 to form bridged 7 (allylpalladium chloride dimer,(tBu)3P, DABCO ) after hydrogenation (H2, Pd).

The second ring-closing step was accomplished by introducing iodine using iodine/oxygen and copper chloride. Here the Butler group explains that in a happy case of serendipitous discovery they found out this reaction required copper catalysis because one phenol batch contained copper residue from a botched coupling reaction. The ring-closing step itself (BOC protection and C-H arylation) required palladium(II) acetate, tricyclohexylphosphine. and pivalic acid in dimethylacetamide.

Yes that is again a lot of palladium and if you agree with this blog that synthetic organic chemistry is converging towards the sole use of palladium, halogens and anything with carbon and hydrogen, this sequence will only strengthen your case.